The fundamental issue of how a schistosome survives, or is targeted for destruction, in a snail host has important implications for the epidemiology of schistosomiasis. Preceding groundwork clearly showed that genetic variations in the snail Biomphalaria glabrata play a major role in the intramolluscan development of the parasitic helminth Schistosoma mansoni. Snail stocks that were genetically selected as either parasite resistant or susceptible have provided us with valuable resources for identifying markers as well as gene(s) important in the snail/parasite relationship. Our objective is to use well-established molecular tools, studying defined snail stocks with stable but different susceptibility phenotypes, to identify and characterize those snail genes that play a critical role in resisting, or fully supporting, a schistosome infection. Polymorphisms in resistant vs. susceptible snail DNA should enable us to efficiently isolate probes targeting those sequences involved in the snail/parasite relationship. Use will also be made of examining the heritability of polymorphic markers in progeny snails that segregate for resistance or susceptibility. By generating suppression subtraction hybridization (SSH) libraries from exposed vs normal resistant and susceptible juvenile snails and, by screening an available snail microarray with cDNA probes from resistant and susceptible juvenile snails (+/- parasite infection), we hope to identify genes that govern these different infection phenotypes in this snail-host. For positional mapping of B. glabrata chromosomes by FISH, we will use (as probes) BAG clones, corresponding to transcripts identified from the microarray/subtraction studies. Our overall strategy is to reduce the inflow of repetitive markers and combine useful information gained at both DNA and RNA levels to dissect relevant gene products involved in parasite development or destruction coded for, within the relatively large B. glabrata genome.